Hypothesis:

Adjunctive treatment with trapidil in patients that have undergone successful ballon angioplasty will reduce the incidence of angiographic restenosis compared to aspirin.

Study Design

Study Design:

Patients Enrolled: 254

Patient Populations:

Age >18 and <75 years with a coronary stenosis at caliper analysis ≥70% amenable to PTCA in no more than two sites and no more than two vessels and documented significant myocardial ischemia (ECG, ECG exercise test, thallium exercise, or dipyridamole stress test).

Exclusions:

Previous myocardial infarction or thrombolytic therapy <15 days earlier, total occlusions, patients with restenotic lesions, patient inability to return for repeat angiogram, Q-wave infarct or akinesia at all sites considered for PTCA, three-vessel or left main coronary disease, women of childbearing potential, hepatic or renal insufficiency, known intolerance to trapidil or aspirin and active peptic disease.

Primary Endpoints:

Restenosis at follow-up coronary angiography, defined as the loss of ≥50% of the gain in luminal diameter accomplished by dilatation (initial gain minus final gain/initial gain x 100). Restenosis was also evaluated by the definition of a final stenosis as ≥50%.

Secondary Endpoints:

Drug/Procedures Used:

Patients received either trapidil 100 mg TID (n=128) or aspirin at the same dosage 100 mg TID (n=126) at least 3 days before angioplasty and for 6 months thereafter. Treatment ceased 6 months after PTCA. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Patients were regularly followed up by each center to obtain clinical information and to perform repeat angiography in case of symptom recurrence. Whenever no restenosis was found at an early nonprotocol angiogram, the angiogram was repeated at 6 months. Treadmill tests (Bruce protocol) were performed 1 month after PTCA and repeated (not mandatory) at 6 months.

Principal Findings:

The two groups were comparable for all clinical characteristics except unstable angina, which was significantly more highly represented in the trapidil group (30.6% versus 18.3%, P<0.05). Restenosis per patient, defined as loss of initial gain >=50%, occurred in 24.2% of patients in the trapidil group and 39.7% in the aspirin group (P<0.01). Restenosis per lesion results were 23.3% in the trapidil group and 36.9% in the aspirin group (P=0.018). By the second definition (final stenosis, >50%), restenosis per patient resulted in a 30.5% rate in the trapidil group versus 45.2% in the aspirin group (P=0.015); restenosis per vessel was 29.6% in the trapidil group and 42.5% in the aspirin group (P=0.023). Clinical follow-up revealed a significantly lower incidence of angina at 6 months in the trapidil group (25.8% versus 43.7%, P<0.01), while other cardiovascular events were similar in the two groups. No deaths were observed in either group. There were no differences in laboratory tests between treatments both at baseline and at 6-month follow-up. Nine patients suffered from acute events and the numbers were comparable in the two groups. There were 12 dropouts for drug adverse reactions, 6 in each group.

Interpretation:

Among patients undergoing coronary angioplasty, treatment with trapidil was associated with a significant reduction in restenosis compared with aspirin. In addition, mean results for percent stenosis at follow-up, final gain, and loss of initial gain confirmed its association with preventing vessel reocclusion.